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March-2015 Volume 33 Issue 3

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Article

Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells

  • Authors:
    • Jung Eun Choi
    • Seon Min Woo
    • Kyoung-Jin Min
    • Su Hwan Kang
    • Soo Jung Lee
    • Taeg Kyu Kwon
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, Keimyung University, School of Medicine, Dalseo-Gu, Daegu 704-701, Republic of Korea, Department of Surgery, Yeungnam University, College of Medicine, Nam‑gu, Daegu 705-703, Republic of Korea
  • Pages: 1395-1401
    |
    Published online on: January 15, 2015
       https://doi.org/10.3892/or.2015.3728
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Abstract

ABT-737, a BH3-mimetic small-molecule inhibitor, binds with very high affinity to Bcl-2, Bcl-xL and Bcl-w, and inhibits their activity. Aurora kinase is one of the serine/threonine kinase family members and is a vital and critical regulator of mitosis and meiosis. In the present study, we investigated the effects and mechanisms of a combined treatment of ABT-737 and VX-680 (Aurora kinase inhibitor) in human breast cancer MDA-MB‑435S cells. ABT-737 plus VX-680 induced caspase-dependent apoptosis in the human breast cancer cells. Combined treatment with ABT-737 and VX-680 led to the downregulation of Bcl-2 expression at the transcriptional level and the downregulation of c-FLIP and Mcl-1 expression at the post-transcriptional level. Overexpression of Bcl-2 or c-FLIP could not block the induction of apoptosis caused by the combined treatment with ABT-737 and VX-680. However, overexpression of Mcl-1 partially inhibited the induction of apoptosis. In contrast, the combined treatment with ABT-737 and VX680 had no effect on the apoptosis in normal cells. Taken together, our study demonstrated that combined treatment with ABT-737 and VX-680 induced apoptosis in anti‑apoptotic protein (Bcl-2 or c-FLIP)-overexpressing cells.
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Copy and paste a formatted citation
Spandidos Publications style
Choi JE, Woo SM, Min K, Kang SH, Lee SJ and Kwon TK: Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells. Oncol Rep 33: 1395-1401, 2015.
APA
Choi, J.E., Woo, S.M., Min, K., Kang, S.H., Lee, S.J., & Kwon, T.K. (2015). Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells. Oncology Reports, 33, 1395-1401. https://doi.org/10.3892/or.2015.3728
MLA
Choi, J. E., Woo, S. M., Min, K., Kang, S. H., Lee, S. J., Kwon, T. K."Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells". Oncology Reports 33.3 (2015): 1395-1401.
Chicago
Choi, J. E., Woo, S. M., Min, K., Kang, S. H., Lee, S. J., Kwon, T. K."Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells". Oncology Reports 33, no. 3 (2015): 1395-1401. https://doi.org/10.3892/or.2015.3728
Copy and paste a formatted citation
x
Spandidos Publications style
Choi JE, Woo SM, Min K, Kang SH, Lee SJ and Kwon TK: Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells. Oncol Rep 33: 1395-1401, 2015.
APA
Choi, J.E., Woo, S.M., Min, K., Kang, S.H., Lee, S.J., & Kwon, T.K. (2015). Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells. Oncology Reports, 33, 1395-1401. https://doi.org/10.3892/or.2015.3728
MLA
Choi, J. E., Woo, S. M., Min, K., Kang, S. H., Lee, S. J., Kwon, T. K."Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells". Oncology Reports 33.3 (2015): 1395-1401.
Chicago
Choi, J. E., Woo, S. M., Min, K., Kang, S. H., Lee, S. J., Kwon, T. K."Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells". Oncology Reports 33, no. 3 (2015): 1395-1401. https://doi.org/10.3892/or.2015.3728
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